乳铁蛋白-聚合物泡囊载S14G-Humanin肽对Amyloid-β25-35诱导的阿尔茨海默病模型大鼠的神经保护作用.docxVIP

乳铁蛋白 -聚合物泡囊载 S14G-Humanin 肽对 Amyloid- β25-35 诱导的阿尔茨海默病模型大鼠的神经保护作用 俞媛 1，冯亮 2，高会乐 2，蒋新国 2* （ 1 第二军医大学药学院药剂学教研室 上海 200433，2 复 旦大学药学院药剂学教研室 上海 200032） 摘要：目的 构建以乳铁蛋白作为靶向功能基、 可生物降解聚合物泡囊为载体的脑靶 向递药系统 ，并 对其 脑部递药 特性 作出 药效学评价。 方法 制备 载神 经肽 S14G-Humanin 的乳铁蛋白－聚合物泡囊并对其进行表征，建立大鼠阿尔茨海默病 模型，采用 Morris 水迷宫试验评价载药系统对大鼠记忆认知障碍的改善。 结果 聚 合物泡囊粒径约 126nm，zeta 电位 -2.54mV，包封率 21.78%，药效学实验表明，载 S14G-Humanin 的聚合物泡囊能够显著改善大鼠的记忆缺陷，同时对 Amyloid- β 25-35 诱导的 Bax 蛋白的过量表达具有抑制作用。 结论 乳铁蛋白连接聚合物泡囊 载药系统能够对多肽药物起到保护作用，提高药物的治疗效果，本递药系统具有较 好的脑内递药特性。 关键词：聚合物泡囊 乳铁蛋白 阿尔茨海默病 中图分类号 : 文献标识码 : 文章编号 : Lactoferrin Conjugated self-assembled Polymer vesicles loaded S14G-Humanin, prevents Amyloid- β25-35 induced memory impairment in rats YU Yuan 1, FENG Liang 2, GAO Hui-le 2, JIANG Xin-guo 2* (1 Department of Pharmaceutics , School of Pharmacy, Second Military Medical University, Shanghai 200433; 2 Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032) ABSTRACT: OBJECTIVE To prepare a novel brain targeting system, lactoferrin conjugated self-assembledpolymer vesicles(Lf-PVs), which the brain delivery property had been evaluated in vivo. METHODS S14G-Humanin (S14G-HN) as a neuroprotective peptide was entrapped within Lactoferrin conjugated self-assembled polymer vesicles by an ammonium sulphate gradients method. The Lf-PVs were characterized for shape, size, electrical charge and entrapment efficiency. Thevivo effect of Lf-PVs contained S14G-HN was examined on amnesia induced by Amyloid- β25-35 in rats. RESULTS The Lf-PVs had a round and vesicle-like shape with a mean diameter around 126 nm by direct cryogenic temperature transmission electron micrograph (Cryo-TEM) and a negative electrical charge(-2.54mV). Coupling of Lf with PVs was confirmed by immuno-gold labeling of Lf visualized under the TEM. The drug entrapment efficiency is 21.78%. S14G-HN encapsulated into Lf-PVs could protect latent learning as well as spatial working memory and inhibit the over-expression of Bax protein in Amyloid- β25